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Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults

BACKGROUND: Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant use...

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Autores principales: Pronk, A. C., Seppala, L. J., Trajanoska, K., Stringa, N., van de Loo, B., de Groot, L. C. P. G. M., van Schoor, N. M., Koskeridis, F., Markozannes, G., Ntzani, E., Uitterlinden, A. G., Rivadeneira, F., Stricker, B. H., van der Velde, N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009709/
https://www.ncbi.nlm.nih.gov/pubmed/35421149
http://dx.doi.org/10.1371/journal.pone.0266590
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author Pronk, A. C.
Seppala, L. J.
Trajanoska, K.
Stringa, N.
van de Loo, B.
de Groot, L. C. P. G. M.
van Schoor, N. M.
Koskeridis, F.
Markozannes, G.
Ntzani, E.
Uitterlinden, A. G.
Rivadeneira, F.
Stricker, B. H.
van der Velde, N.
author_facet Pronk, A. C.
Seppala, L. J.
Trajanoska, K.
Stringa, N.
van de Loo, B.
de Groot, L. C. P. G. M.
van Schoor, N. M.
Koskeridis, F.
Markozannes, G.
Ntzani, E.
Uitterlinden, A. G.
Rivadeneira, F.
Stricker, B. H.
van der Velde, N.
author_sort Pronk, A. C.
collection PubMed
description BACKGROUND: Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. METHODS: The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. RESULTS: In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26–0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17–3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07–2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05–3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01–1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92–1.00). CONCLUSION: This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.
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spelling pubmed-90097092022-04-15 Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults Pronk, A. C. Seppala, L. J. Trajanoska, K. Stringa, N. van de Loo, B. de Groot, L. C. P. G. M. van Schoor, N. M. Koskeridis, F. Markozannes, G. Ntzani, E. Uitterlinden, A. G. Rivadeneira, F. Stricker, B. H. van der Velde, N. PLoS One Research Article BACKGROUND: Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. METHODS: The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. RESULTS: In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26–0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17–3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07–2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05–3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01–1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92–1.00). CONCLUSION: This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention. Public Library of Science 2022-04-14 /pmc/articles/PMC9009709/ /pubmed/35421149 http://dx.doi.org/10.1371/journal.pone.0266590 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Pronk, A. C.
Seppala, L. J.
Trajanoska, K.
Stringa, N.
van de Loo, B.
de Groot, L. C. P. G. M.
van Schoor, N. M.
Koskeridis, F.
Markozannes, G.
Ntzani, E.
Uitterlinden, A. G.
Rivadeneira, F.
Stricker, B. H.
van der Velde, N.
Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
title Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
title_full Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
title_fullStr Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
title_full_unstemmed Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
title_short Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
title_sort candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009709/
https://www.ncbi.nlm.nih.gov/pubmed/35421149
http://dx.doi.org/10.1371/journal.pone.0266590
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